Kisspeptin: Role in reproduction and implications for infertility management

Sir,

Kisspeptins are a family of peptide hormones, which play a critical role in reproduction. They are found in the gonads, nervous system, anterior pituitary, and the placenta toward term. Kisspeptin receptor is a G-protein-coupled receptor found in the central nervous system, anterior pituitary, and the placenta.[1] The kisspeptin acts through its receptor and brings about a release of predominantly Luteinizing Hormone(LH) from the anterior pituitary. The role of kisspeptin in bringing about the mid-cycle LH surge in response to increasing estradiol is being recognized based on rodent studies.[2] Knockout Mice for kisspeptin receptor fail to mount an LH surge. Differential effect of estrogen on KISS 1 secreting neurons in the hypothalamic arcuate nucleus and in the hypothalamic anteroventral periventricular nuclear is responsible for the variable effect of estrogen on the pituitary secretion of gonadotrophins.

Kisspeptin is also involved in the link between nutritional status and fertility through its interaction with leptin, another peptide that is important in regulation of appetite and body weight.[1]

Kisspeptin may provide unique therapies for infertility. It provokes a rise in LH on subcutaneous infusion in normo-ovulatory women especially in the preovulatory phase. Women with hypothalamic amenorrhea show a rise in gonadotrophin level on biweekly injection of kisspeptin.[3] Gonadotrophins are the mainstay of treatment of subfertility at present. They are expensive and can lead to ovarian hyperstimulation syndrome and multiple gestations. The cost of gonadotrophins is prohibitive. Kisspeptin, because of its role in regulating the hypothalamo-pituitary-gonadal axis and causing gonadotrophin release, can be an important therapeutic option in subfertility. Cases of delayed puberty and hypogonadotropic hypogonadism are conditions where administration of kisspeptin shows promise. In addition, tropic action on LH release can be utilized in triggering ovulation in cases of intra-uterine Insemination and in-vitro fertilization cycles. Further study of interaction of kisspeptin with other ligands like leptin and neurokinin B may reveal newer insights into regulation of reproduction and pave way for better therapeutic options for infertility.